We have undertaken a project in collaboration with colleagues in Stanford University School of Medicine to study peptides derived from MHC molecules which exhibit interesting immunomodulatory properties. The long-term goals of this effort are to understand in detail the basis for induction of T cell tolerization by these peptides, and also to develop potential candidates for use in human clinical immunsuppressive therapy. Our role is to carry out a structure/function analysis of MHC-derived peptides in order to determine the structural elements that are necessary and sufficient for immunosuppressive activity. To date, we have found, through a "serine scane" amino acid residues of a base sequence dodecapeptide which are critical for activity. One of these derivatives, and two other analogs have activity superior to that of the parent sequence. We plan to continue these studies, and to use tagged peptides as affinity ligands for receptor purification and biophysical characterization. FAB-MS is n invaluable tool for confirming the structure of the peptides and peptide derivatives that we synthesize in this work.